κ-Opioid receptor stimulation modulates TLR4/NF-κB signaling in the rat heart subjected to ischemia–reperfusion

Lin, Ji; Wang, Haiyan; Li, Juan; Wang, Qianmei; Zhang, Shumiao; Feng, Na; Fan, Rong; Pei, Jianming

doi:10.1016/j.cyto.2013.01.002

Cited by 35 publications

(28 citation statements)

References 46 publications

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“…Wu et al reported that U50,488H administration could inhibit neutrophil accumulation and TNF-α induction in myocardium subjected to ischemia/reperfusion [52]. Lin et al reported that U50,488H administration could inhibit TLR4/NF-κB signaling induced by ischemia/reperfusion in rats hearts [30]. In this study, we found that treatment with U50,488H inhibited DM-induced IL-6, IL-8 and sICAM-1 production.…”

Section: Discussionsupporting

confidence: 62%

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Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats

et al. 2015

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BackgroundEvidence suggests that activation of κ-opioid receptor (KOR) by U50,488H exhibits potential cardiovascular protective properties. However, the effects of U50,488H on vascular dysfunction in diabetes mellitus (DM) are still not clear. The present study was designed to investigate the effects of U50,488H on vascular dysfunction in diabetic rats and explore the underlying mechanisms involved.MethodsRats were randomly divided into control, DM, DM + vehicle, DM + U50,488H and DM + nor-binaltorphimine (nor-BNI) groups. Streptozotocin injection was used to induce DM. Weight, blood glucose, blood pressure and plasma insulin for each group were measured. Arterial functions were assessed with isolated vessels mounted for isometric tension recordings. Angiotensin II (ANG II), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and IL-8 levels were measured by ELISA, and endothelial nitric oxide synthase (eNOS) phosphorylation and NF-κB p65 translocation were measured by Western blot.ResultsActivation of KOR by U50,488H reduced the enhanced contractility of aortas to KCl and noradrenaline and increased acetylcholine-induced vascular relaxation, which could also protect the aortal ultrastructure in DM. U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment. Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment.ConclusionsOur study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

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Section: Discussionsupporting

confidence: 62%

“…It has been recognized that NF-κB signaling plays an important role in inflammation in many diseases. Recent studies also reveal that NF-κB signaling may be involved in the KOR activation-offered protective effects [29,30]. …”

Section: Introductionmentioning

confidence: 99%

Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats

et al. 2015

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“…Our current data demonstrate that the KOR agonist U50,488H activated the cAMP/CREB signaling pathway in chondrocytes, which is in accordance with the previously published report indicating an increase in cAMP concentration after treatment with dynorphin A in splenic phagocytes (37). It is well established that KOR activation exerts antiinflammatory effects by reducing production of interleukins in many cells types, such as cardiomyocytes (38), monocytes (39), and alveolar osteoclasts (40). KOR expression was also reported in normal synovial fibroblasts and its expression was suppressed under pathological conditions like rheumatic arthritis or OA (41).…”

Section: Discussionmentioning

confidence: 99%

Kappa opioid receptor signaling protects cartilage tissue against posttraumatic degeneration

Wu¹,

Zhang²,

Shkhyan³

et al. 2017

JCI Insight

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“…TLRs are a family of molecules that play a critical role in the regulation of innate immunity, which is a significant component of myocardial I/R (MI/R) injury. When inhibited, TLRs protect against MI/R-induced damage in the heart (3,22). Therefore, the authors hypothesized that the anti-apoptotic action of carvedilol may be associated with a TLR4/NF-κB-mediated response.…”

Section: Discussionmentioning

confidence: 99%

“…There are a number of signaling pathways that participate in cardiomyocyte apoptosis; however, the toll-like receptor 4 (TLR4)/nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signal pathway is known to play one of the key roles in I/R injury (3,4) and has been observed to become markedly upregulated in failing and ischemic myocardium (5). Conversely, TLR4 deficiency increases the survival rate of cardiomyocytes following myocardial ischemia via an apoptosis-mediated effect (6).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective effect of carvedilol: inhibition of apoptosis in H9c2 cardiomyocytes via the TLR4/NF-κB pathway following ischemia/reperfusion injury

Zhao

Yan

Zhang

et al. 2014

Experimental and Therapeutic Medicine

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Carvedilol is a non-selective β-blocker used in the treatment of cardiovascular disease, including myocardial ischemia. The aim of the present study was to investigate the molecular mechanisms underlying the effects of carvedilol on simulated ischemia/reperfusion (SI/R)-induced cardiomyocyte apoptosis in vitro. H9c2 cardiomyocytes were incubated with either a vehicle or an ischemic buffer during hypoxia followed by reoxygenation with or without carvedilol. In two additional groups, toll-like receptor 4 (TLR4) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were inhibited by a TLR4 antibody and pyrrolidine dithiocarbamate, respectively. The results revealed that carvedilol markedly decreased SI/R-induced apoptosis in a concentration-dependent manner, as demonstrated by flow-cytometric analysis. This effect was shown to be associated with an increase in the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax) protein ratio and concurrent reductions in the expression levels of TLR4 and NF-κB. These results suggest that carvedilol provides significant cardioprotection against SI/R-induced injury in H9c2 cardiomyocytes, an effect likely to be mediated through the TLR4/NF-κB signaling pathway.

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κ-Opioid receptor stimulation modulates TLR4/NF-κB signaling in the rat heart subjected to ischemia–reperfusion

Cited by 35 publications

References 46 publications

Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats

Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats

Kappa opioid receptor signaling protects cartilage tissue against posttraumatic degeneration

Cardioprotective effect of carvedilol: inhibition of apoptosis in H9c2 cardiomyocytes via the TLR4/NF-κB pathway following ischemia/reperfusion injury

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